Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with unpredictable course, with periods of flares and remission. SLE is characterized by a broad spectrum of clinical manifestations and varying patterns of disease activity. The efficacy of current SLE medication has been questioned by treatment-related adverse side effects secondary to corticosteroid use and untargeted immunosuppression and by the increasing number of patients with refractory disease. Over the last decades, there has been major progress in the understanding of the immunopathology of SLE, paving the way for the development of new biological agents, potentially revolutionizing the treatment of SLE. A variety of novel therapeutic targets have been identified and there have been many studies in patients with SLE in an attempt to translate these new treatments into clinical practice.